Vitamin A Metabolism in Rod and Cone Visual Cycles

Saari, John C.

doi:10.1146/annurev-nutr-071811-150748

Cited by 159 publications

(135 citation statements)

References 125 publications

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“…Detoxification of arylalkylamines in photodetectors is thought to be important, because arylalkylamines can complex with and inactivate retinaldehyde, an essential component of light capture (38). Other retinaldehyde-related genes are also thought to have appeared as a result of duplication and neofunctionalization including an isomerase (Rpe65), retinoid metabolizing enzymes (Rdh5, Rhd8, Rdh12, and Lrat), and retinoid binding proteins (Rlbp1 and Rbp3) (39).…”

Section: Discussionmentioning

confidence: 99%

Drastic neofunctionalization associated with evolution of the timezyme AANAT 500 Mya

Falcón

Coon

Besseau

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Melatonin (N-acetyl-5-methoxytrypamine) is the vertebrate hormone of the night: circulating levels at night are markedly higher than day levels. This increase is driven by precisely regulated increases in acetylation of serotonin in the pineal gland by arylalkylamine N-acetyltransferase (AANAT), the penultimate enzyme in the synthesis of melatonin. This unique essential role of AANAT in vertebrate timekeeping is recognized by the moniker the timezyme. AANAT is also found in the retina, where melatonin is thought to play a paracrine role. Here, we focused on the evolution of AANAT in early vertebrates. AANATs from Agnathans (lamprey) and Chondrichthyes (catshark and elephant shark) were cloned, and it was found that pineal glands and retinas from these groups express a form of AANAT that is compositionally, biochemically, and kinetically similar to AANATs found in bony vertebrates (VT-AANAT). Examination of the available genomes indicates that VT-AANAT is absent from other forms of life, including the Cephalochordate amphioxus. Phylogenetic analysis and evolutionary rate estimation indicate that VT-AANAT evolved from the nonvertebrate form of AANAT after the Cephalochordate-Vertebrate split over one-half billion years ago. The emergence of VT-AANAT apparently involved a dramatic acceleration of evolution that accompanied neofunctionalization after a duplication of the nonvertebrate AANAT gene. This scenario is consistent with the hypotheses that the advent of VT-AANAT contributed to the evolution of the pineal gland and lateral eyes from a common ancestral photodetector and that it was not a posthoc recruitment.E yes have evolved in all animals to facilitate interactions with the photic environment (1, 2). However, among animals, vertebrates are unique in that they also possess a photoneuroendocrine structure, the pineal gland (3). It converts the 24-h rhythm in environmental lighting into a 24-h rhythm in circulating melatonin, thereby providing a unique and valuable signal of the photic environment. The details of pineal evolution are not clear (4, 5). However, it has been posited that an essential element was arylalkylamine N-acetyltransferase (AANAT; E.C. 2.3.1.87), the penultimate enzyme in the melatonin biosynthesis pathway (6-8); this scenario is referred to as the AANAT hypothesis of pineal evolution (7,8).AANAT catalyzes the N-acetylation of arylalkylamines using acetyl CoA (AcCoA) as the acetyl group donor. The AANAT family, which belongs to the GCN5 superfamily (9, 10), is composed of two subfamilies termed vertebrate (VT) AANAT and nonvertebrate (NV) AANAT. † This nomenclature reflects the phylogenetic distribution of the family members (13-17). The most striking differences between VT-and NV-AANAT are found in regulatory and catalytic regions of the encoded proteins (Fig. 1), consistent with different metabolic roles (7,8).The NV-AANAT is thought to perform a detoxification function through acetylation of a broad range of endogenous and exogenous arylalkylamines and polyamines (13-16). It has been fo...

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Section: Discussionmentioning

confidence: 99%

Drastic neofunctionalization associated with evolution of the timezyme AANAT 500 Mya

Falcón

Coon

Besseau

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…This process, known as the visual cycle, requires export of the alltrans chromophore out of the photoreceptors and its conversion to the 11-cis form in retinal pigment epithelial (RPE) cells (for both rods and cones) or in retinal Müller glia (for cones only). The 11-cis chromophore is then imported back into photoreceptors, where it combines with a molecule of free opsin to regenerate the visual pigment (1,2). The cone-specific visual cycle (3) has been suggested to enable cones, but not rods, to quickly recover from bright light exposure and to function over a wide range of light intensities (4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

CRALBP supports the mammalian retinal visual cycle and cone vision

et al. 2015

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“…T he visual cycle plays a crucial role in the removal of all-transretinal from photoreceptor cells following photoexcitation and its conversion to 11-cis-retinal for the regeneration of visual pigments in rod and cone photoreceptor cells (1). Deficient clearance of all-trans-retinal and its Schiff-base conjugate N-retinylidenephosphatidylethanolamine (PE) from rod and cone photoreceptor outer segments results in condensation reactions which produce a mixture of bisretinoid products including the pyridinium bisretinoid compound A2PE and its hydrolytic product A2E (2,3).…”

mentioning

confidence: 99%

ATP-binding cassette transporter ABCA4 and chemical isomerization protect photoreceptor cells from the toxic accumulation of excess 11- cis -retinal

Quazi

Molday

2014

Proc. Natl. Acad. Sci. U.S.A.

113

101

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The visual cycle is a series of enzyme-catalyzed reactions which converts all-trans-retinal to 11-cis-retinal for the regeneration of visual pigments in rod and cone photoreceptor cells. Although essential for vision, 11-cis-retinal like all-trans-retinal is highly toxic due to its highly reactive aldehyde group and has to be detoxified by either reduction to retinol or sequestration within retinal-binding proteins. Previous studies have focused on the role of the ATP-binding cassette transporter ABCA4 associated with Stargardt macular degeneration and retinol dehydrogenases (RDH) in the clearance of all-trans-retinal from photoreceptors following photoexcitation. How rod and cone cells prevent the accumulation of 11-cis-retinal in photoreceptor disk membranes in excess of what is required for visual pigment regeneration is not known. Here we show that ABCA4 can transport N-11-cis-retinylidene-phosphatidylethanolamine (PE), the Schiff-base conjugate of 11-cis-retinal and PE, from the lumen to the cytoplasmic leaflet of disk membranes. This transport function together with chemical isomerization to its all-trans isomer and reduction to all-trans-retinol by RDH can prevent the accumulation of excess 11-cis-retinal and its Schiff-base conjugate and the formation of toxic bisretinoid compounds as found in ABCA4-deficient mice and individuals with Stargardt macular degeneration. This segment of the visual cycle in which excess 11-cis-retinal is converted to all-transretinol provides a rationale for the unusually high content of PE and its long-chain unsaturated docosahexaenoyl group in photoreceptor membranes and adds insight into the molecular mechanisms responsible for Stargardt macular degeneration.T he visual cycle plays a crucial role in the removal of all-transretinal from photoreceptor cells following photoexcitation and its conversion to 11-cis-retinal for the regeneration of visual pigments in rod and cone photoreceptor cells (1). Deficient clearance of all-trans-retinal and its Schiff-base conjugate N-retinylidenephosphatidylethanolamine (PE) from rod and cone photoreceptor outer segments results in condensation reactions which produce a mixture of bisretinoid products including the pyridinium bisretinoid compound A2PE and its hydrolytic product A2E (2, 3). These bisretinoid compounds accumulate as lipofuscin deposits in retinal pigment epithelial (RPE) cells upon phagocytosis of outer segments and have been implicated in the pathology of a number of retinal degenerative diseases. This is particularly evident in autosomal recessive Stargardt macular degeneration in which mutations in the ATP-binding cassette (ABC) transporter ABCA4 which impair the N-retinylidene-PE transport activity of ABCA4 cause a buildup of lipofuscin, atrophy of the central retina, and severe progressive loss in vision (4-8).In initial studies, Abca4 knockout mice were reported to show a light-dependent accumulation of all-trans-retinal, PE, and N-retinylidene-PE in photoreceptors and lipofuscin and A2E in RPE (9). This led to a model...

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Vitamin A Metabolism in Rod and Cone Visual Cycles

Cited by 159 publications

References 125 publications

Drastic neofunctionalization associated with evolution of the timezyme AANAT 500 Mya

Drastic neofunctionalization associated with evolution of the timezyme AANAT 500 Mya

CRALBP supports the mammalian retinal visual cycle and cone vision

ATP-binding cassette transporter ABCA4 and chemical isomerization protect photoreceptor cells from the toxic accumulation of excess 11- cis -retinal

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